Fabrication and characterization of PLGA loaded nanoparticles of Umbelliferone β-d-galactopyranoside in the treatment of lipopolysaccharide-induced acute lung inflammation via PI3K/Akt/Mtor pathway = Fabrication and characterization of PLGA loaded nanoparticles of Umbelliferone β-d-galactopyranoside in the treatment of lipopolysaccharide-induced acute lung inflammation via PI3K/Akt/Mtor pathway

다국어 초록 (Multilingual Abstract)

Purpose: Acute Lung injury (ALI) which is included by a strong pulmonary inflammation and its causes the mortality and morbidity in critically ill patients. Phosphoinositide 3- kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathways is consider as the singling pathway, who activates the diverse cellular function viz., survival, cell expansion, vesicular transport and proliferation. Umbelliferone β-d-galactopyranoside (UFG) plays an important protective role in the expansion of inflammation, oxidative stress and cancer. The present research was initiated to develop a suitable delivery system for UFG with an intention to enhance its therapeutic efficacy against acute lung inflammation induced lipopolysaccharide in mice via alteration of PI3K/Akt/Mtor inhibitor. Methods: UFG-loaded polymeric nanoparticles prepared by sonication were scrutinized for average size, zeta potential, and drug release potency in animals. The rodent was divided into different groups and counted in the bronchoalveolar lavage fluid (BALF). Antioxidant parameters and proinflammatory cytokines were measured. The concentration of PI3K, P-PI3K, mTOR, P-mTOR Akt and P-Akt were determined, respectively. Result: UFG-loaded poly(d,l-lactide-co-glycolide) nanoparticles (UFG-PLGA-NP) with particle size of 187.1 nm and polydispersity index 0.16 were uniform in nature with 82.5% release of the total amount of drug after 48 h. UFG marked suppressed the inflammation number in the BALF (78.5%) as well as reduced the oxidative stress via improved the status of endogenous antioxidant parameters such as SOD (45.5%) and MPO (53.4%); pro-inflammatory cytokines viz., TNF-α (442.3%), IL-6 (48.3%) and IL-1β (54.4%) . ALI control group mice confirmed the change protein levels of PI3K/Akt/mTOR pathway in lung as compared to normal control, which was significantly down-regulated by the UFG-PLGA-NPs. In the histological study, we found that the UFG-PLGA-NPs substantially reduced the LPS-induced neutrophils in lung tissue. Conclusion: UFG-PLGA-NPs attenuating the acute lung inflammation developed during the LPS induced lung cancer via play an effective role to inhibit the PI3K/Akt/mTOR pathway.